On the role of CD4+ T cells in the CD8+ T-cell response elicited by recombinant adenovirus vaccines

Abstract

We have investigated the role of CD4+ T cells in the development of the CD8+ T-cell response after immunization with recombinant adenovirus (rAd). In the absence of CD4+ T cells, the "unhelped" CD8+ T-cell population exhibited a reduction in primary expansion and long-term survival that appeared to be due to inadequate priming of naïve T cells. There were few functional or phenotypic differences between the helped and unhelped CD8+ T-cell populations with the exception of O-glycosylated CD43, a marker of effector cells, which was augmented on the unhelped CD8+ T-cell population. In some cases, the unhelped CD8+ T-cell population exhibited reduced ability to control virus infection; however, this appeared to be a function of the reduced frequency of antigen-specific CD8+ T cells. Most notably, the unhelped CD8+ T-cell population exhibited no defect in secondary expansion. These results provide insight into the role of CD4+ T cells during the primary CD8+ T-cell response generated by rAd vaccines and identify potential benefits and issues that must be considered when using adenovirus vaccines under conditions where CD4+ T-cell function may be limiting, such as vaccination of human immunodeficiency virus patients.